Reactome | UniProt:Q99758 ABCA3

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UniProt:Q99758 ABCA3 Show undefined attributes

chain	chain:1-1704 chain:175-1704
checksum	606735C504839D0D
comment	FUNCTION Catalyzes the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar bodies biogenesis and homeostasis of pulmonary surfactant (PubMed:16959783, PubMed:17574245, PubMed:27177387, PubMed:28887056, PubMed:31473345). Transports preferentially phosphatidylcholine containing short acyl chains (PubMed:27177387). In addition plays a role as an efflux transporter of miltefosine across macrophage membranes and free cholesterol (FC) through intralumenal vesicles by removing FC from the cell as a component of surfactant and protects cells from free cholesterol toxicity (PubMed:25817392, PubMed:26903515, PubMed:27177387).CATALYTIC ACTIVITY ATP + H2O + xenobioticSide 1 = ADP + phosphate + xenobioticSide 2.CATALYTIC ACTIVITY a 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ADP + phosphate + H(+)CATALYTIC ACTIVITY ATP + H2O + phospholipidSide 1 = ADP + phosphate + phospholipidSide 2.CATALYTIC ACTIVITY 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine(in) + ATP + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine(out) + ADP + phosphate + H(+)CATALYTIC ACTIVITY cholesterol(in) + ATP + H2O = cholesterol(out) + ADP + phosphate + H(+)CATALYTIC ACTIVITY a 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol)(in) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol)(out) + ADP + phosphate + H(+)ACTIVITY REGULATION The ATP-dependent phosphatidylcholine transport is competitively inhibited by miltefosine.SUBUNIT Homooligomer; disulfide-linked.SUBCELLULAR LOCATION Localized in the limiting membrane of lamellar bodies in lung alveolar type II cells (PubMed:11718719, PubMed:16959783, PubMed:22673903, PubMed:24142515, PubMed:27177387). Trafficks via the Golgi, sorting vesicles (SVs) and late endosome/multivesicular body network directly to the outer membrane of lamellar bodies in AT2 lung epithelial cells or to lysosomes and lysosomal-related organelles (LROs) in other cells where undergoes proteolytic cleavage and oligosaccharide processing from high mannose type to complex type (PubMed:16959783, PubMed:20863830, PubMed:24142515, PubMed:27177387). Oligomers formation takes place in a post-endoplasmic reticulum compartment (PubMed:27352740).ALTERNATIVE PRODUCTS Expressed in brain, pancreas, skeletal muscle and heart (PubMed:8706931). Highly expressed in the lung in an AT2-cell-specific manner (PubMed:11718719, PubMed:8706931). Weakly expressed in placenta, kidney and liver (PubMed:8706931). Also expressed in medullary thyroid carcinoma cells (MTC) and in C-cell carcinoma (PubMed:8706931).INDUCTION Up-regulated in Leishmania Viannia (L.V.) panamensis-infected macrophages exposed to miltefosine (PubMed:26903515). Down-regulated by L.V.panamensis infection (PubMed:26903515).DOMAIN Multifunctional polypeptide with two homologous halves, each containing a hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.PTM N-glycosylated (PubMed:16959783, PubMed:24142515, PubMed:27177387). Localization at intracellular vesicles is accompanied by processing of oligosaccharide from high mannose type to complex type (PubMed:16959783, PubMed:27177387). N-linked glycosylation at Asn-124 and Asn-140 is required for stability and efficient anterograde trafficking and prevents from proteasomal degradation (PubMed:24142515).PTM Proteolytically cleaved by CTSL and to a lower extent by CTSB within multivesicular bodies (MVB) and lamellar bodies (LB) leading to a mature form of 150 kDa.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the ABC transporter superfamily. ABCA family.ONLINE INFORMATION Database for mutations in ABC proteins
crossReference	[DatabaseIdentifier:11444205] ENSEMBL:ENSG00000167972 [DatabaseIdentifier:12308469] RefSeq:NP_001080.2 [DatabaseIdentifier:12280907] Pharos - Targets:Q99758 [DatabaseIdentifier:12238130] PRO:Q99758 [DatabaseIdentifier:12149757] PDB:7W02 [DatabaseIdentifier:12149758] PDB:7W01 [DatabaseIdentifier:12135708] Orphanet:ABCA3 [DatabaseIdentifier:12120571] OpenTargets:ENSG00000167972 [DatabaseIdentifier:11530476] ENSEMBL:ENSP00000301732 [DatabaseIdentifier:11530477] ENSEMBL:ENSP00000454397 [DatabaseIdentifier:11653176] ENSEMBL:ENST00000567910 [DatabaseIdentifier:11653175] ENSEMBL:ENST00000301732 [DatabaseIdentifier:11780075] Guide to Pharmacology - Targets:758 [DatabaseIdentifier:11782992] GeneCards:ABCA3 [DatabaseIdentifier:11798630] GlyGen:Q99758 [DatabaseIdentifier:11830478] HMDB Protein:HMDBP13945 [DatabaseIdentifier:11836102] HPA:ENSG00000167972-ABCA3
databaseName	UniProt
dbId	49416
description	recommendedName: fullName evidence="26"Phospholipid-transporting ATPase ABCA3 ecNumber evidence="11 21 22"7.6.2.1 alternativeName: ABC-C transporter alternativeName: fullName evidence="26"ATP-binding cassette sub-family A member 3 alternativeName: ATP-binding cassette transporter 3 shortName: ATP-binding cassette 3 alternativeName: fullName evidence="26"Xenobiotic-transporting ATPase ABCA3 ecNumber evidence="27"7.6.2.2 component recommendedName: fullName evidence="28"150 Kda mature form /component
displayName	UniProt:Q99758 ABCA3
geneName	ABCA3 ABC3
identifier	Q99758
isSequenceChanged	false
keyword	3D-structure Alternative splicing ATP-binding Cytoplasmic vesicle Disease variant Disulfide bond Endosome Glycoprotein Lipid transport Lysosome Membrane Nucleotide-binding Proteomics identification Reference proteome Repeat Translocase Transmembrane Transmembrane helix Transport
modified	[InstanceEdit:9948485] Weiser, Joel, 2025-05-21
moleculeType	Protein
name	ABCA3
otherIdentifier	11723350_a_at 11723351_a_at 11744856_a_at 16823109 204343_PM_at 204343_at 21 35183_at 3644741 3644765 3644766 3676764 3676765 3676766 3676768 3676769 3676770 3676771 3676772 3676773 3676774 3676775 3676779 3676780 3676782 3676783 3676785 3676787 3676789 3676790 3676791 3676793 3676795 3676796 3676799 3676801 3676802 3676804 3676806 3676807 3676812 3676813 3676814 3676815 3676817 3676819 3676820 3676821 3676822 3676823 3676825 3676826 3676827 3676828 3676829 3676830 3676831 3676839 3676840 3676841 3862024 7998784 A_23_P140876 GE59432 GO:0000166 GO:0005215 GO:0005319 GO:0005524 GO:0005615 GO:0005737 GO:0005764 GO:0005765 GO:0005768 GO:0005770 GO:0005886 GO:0006629 GO:0006855 GO:0006869 GO:0008559 GO:0009410 GO:0010875 GO:0012505 GO:0015914 GO:0016020 GO:0016787 GO:0016887 GO:0030324 GO:0030659 GO:0031410 GO:0031902 GO:0032368 GO:0032464 GO:0032585 GO:0034204 GO:0042599 GO:0042626 GO:0042908 GO:0043129 GO:0046470 GO:0046471 GO:0046618 GO:0046890 GO:0048856 GO:0051384 GO:0055085 GO:0055091 GO:0061024 GO:0070925 GO:0097208 GO:0097232 GO:0097233 GO:0120009 GO:0120019 GO:0140326 GO:0140345 GO:0140359 GO:0140657 GO:0150172 GO:1902995 GO:2001140 HMNXSV003041733 ILMN_1758523 PH_hs_0002351 PH_hs_0035220 TC16000783.hg U78735_at g4501848_3p_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-1369005] ABCA3 [lamellar body membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5688390] ABCA3 T1114M [lamellar body membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5688388] ABCA3 N568D [lamellar body membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5688389] ABCA3 E690K [lamellar body membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5688394] ABCA3 E292V [lamellar body membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5683671] ABCA3 L1553P [lamellar body membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5683666] ABCA3 L326P [lamellar body membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5683697] ABCA3 D253H [lamellar body membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5683658] ABCA3 L101P [lamellar body membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5683691] ABCA3 W1142* [lamellar body membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5683705] ABCA3 T1173R [lamellar body membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:12106366] OMIM:601615 ABCA3 [ReferenceDNASequence:12721557] UCSC:Q99758 ABCA3 [ReferenceDNASequence:ensembl:ENSG00000167972] ENSEMBL:ENSG00000167972 ABCA3 [ReferenceDNASequence:11309831] BioGPS Gene:21 ABCA3 [ReferenceDNASequence:11397255] COSMIC - genes:ABCA3 ABCA3 [ReferenceDNASequence:11406543] CTD Gene:21 ABCA3 [ReferenceDNASequence:11433911] dbSNP Gene:21 ABCA3 [ReferenceDNASequence:11814603] HGNC:33 ABCA3 [ReferenceDNASequence:11853558] KEGG:hsa:21 ABCA3 [ReferenceDNASequence:11939620] Monarch:21 ABCA3 [ReferenceDNASequence:12023713] NCBI Gene:21 ABCA3
referenceTranscript	[ReferenceRNASequence:12490579] RefSeq:NM_001089.3 ABCA3
schemaClass	ReferenceGeneProduct
secondaryIdentifier	ABCA3_HUMAN B2RU09 Q54A95 Q6P5P9 Q92473
sequenceLength	1704
species	[Species:48887] Homo sapiens
stId	uniprot:Q99758
url	http://purl.uniprot.org/uniprot/Q99758

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-1369005] ABCA3 [lamellar body membrane] [EntityWithAccessionedSequence:R-HSA-5688390] ABCA3 T1114M [lamellar body membrane] [EntityWithAccessionedSequence:R-HSA-5688388] ABCA3 N568D [lamellar body membrane] [EntityWithAccessionedSequence:R-HSA-5688389] ABCA3 E690K [lamellar body membrane] [EntityWithAccessionedSequence:R-HSA-5688394] ABCA3 E292V [lamellar body membrane] [EntityWithAccessionedSequence:R-HSA-5683671] ABCA3 L1553P [lamellar body membrane] [EntityWithAccessionedSequence:R-HSA-5683666] ABCA3 L326P [lamellar body membrane] [EntityWithAccessionedSequence:R-HSA-5683697] ABCA3 D253H [lamellar body membrane] [EntityWithAccessionedSequence:R-HSA-5683658] ABCA3 L101P [lamellar body membrane] [EntityWithAccessionedSequence:R-HSA-5683691] ABCA3 W1142* [lamellar body membrane] [EntityWithAccessionedSequence:R-HSA-5683705] ABCA3 T1173R [lamellar body membrane]
(referenceSequence)	[ReplacedResidue:5688382] L-threonine 1114 replaced with L-methionine [ReplacedResidue:5688405] L-asparagine 568 replaced with L-aspartic acid [ReplacedResidue:5688381] L-glutamic acid 690 replaced with L-lysine [ReplacedResidue:5688384] L-glutamic acid 292 replaced with L-valine [ReplacedResidue:5683682] L-leucine 1553 replaced with L-proline [ReplacedResidue:5683695] L-leucine 326 replaced with L-proline [ReplacedResidue:5683674] L-aspartic acid 253 replaced with L-histidine [ReplacedResidue:5683659] L-leucine 101 replaced with L-proline [NonsenseMutation:5683690] Nonsense mutation at L-tryptophan 1142 [ReplacedResidue:5683668] L-threonine 1173 replaced with L-arginine
(interactor)	[UndirectedInteraction:11306237] UniProt:Q99758 <-> UniProt:Q8IZF4 (IntAct) [UndirectedInteraction:11306239] UniProt:Q99758 <-> UniProt:Q96GX1 (IntAct) [UndirectedInteraction:11306241] UniProt:Q99758 <-> UniProt:Q9NQ34 (IntAct) [UndirectedInteraction:11306243] UniProt:Q99758 <-> UniProt:Q8WWF5 (IntAct) [UndirectedInteraction:11306245] UniProt:Q99758 <-> UniProt:Q8TDD5 (IntAct) [UndirectedInteraction:11306247] UniProt:Q99758 <-> UniProt:Q86WS5 (IntAct) [UndirectedInteraction:11306249] UniProt:Q99758 <-> UniProt:Q07001 (IntAct)